Growth, development, and regeneration of three types of fetal mouse neurons will be studied in vitro in relation to mechanisms underlying the formation of regionally organized synaptic networks in spcific CNS target tissues: a) dorsal root ganglion (DRG) cells co-cultured with dorsal-horn regions of spinal cord or dorsal-column nuclei of medulla; b) retinal ganglion cells co-cultured with superior colliculus explants; c) monoaminergic brain-stem neurons (e.g. locus coeruleus) co-cultured with explants of hippocampus, iris, and other tissues. In some of these studies, suspensions of dissociated CNS target neurons will be introduced into previously established cultures of organized explants. DRG, retinal, and aminergic neurons will also be co-cultured with carefully positioned pairs of well-defined target and non-target CNS tissues, in extension of our competition experiments with separate explants of dorsal and ventral cord presented to isolated DRGs. Coordinated electrophysiologic, pharmacologic, and cytologic analyses will be carried out during development of these three types of co-cultures to study mechanisms involved in: a) preferential growth of DRG, retinal, and aminergic neurites in relation to target and non-target tissues; b) formation of specific functional synaptic connections with CNS target neurons; c) positional and phenotypic specificity properties which may be encoded in these arrays of co-cultured neurons. The developmental studies in co-cultures of fetal tissues will be extended to problems in CNS regneration by: a) delayed presentation of fetal CNS target tissues until the DRG, retinal, and monoaminergic neurons have matured for several weeks in culture, or vice versa; b) selective microsurgical lesions after maturation in co-culture to permit studies of the relative capacity for regeneration of specific connections.